Renal function is an important determinant of both ischemic and bleeding risk in patients with atrial fibrillation (AF) receiving antithrombotic therapy. A prespecified analysis of the EPIC-CAD randomized trial, published in EuroIntervention, evaluated the impact of renal dysfunction and compared edoxaban monotherapy with dual antithrombotic therapy (edoxaban plus a single antiplatelet agent) in patients with AF and stable coronary artery disease (CAD). 

A total of 1,040 patients were randomized and stratified by creatinine clearance (CrCl) into low (<50 mL/min) and high (≥50 mL/min) groups according to edoxaban dose-reduction criteria. The primary endpoint was net adverse clinical events (NACE), defined as a composite of all-cause death, myocardial infarction, stroke, systemic embolism, urgent revascularization, or major/clinically relevant non-major bleeding at 12 months.

Among the cohort, 252 patients (24.2%) had low CrCl, and 788 (75.8%) had high CrCl. Patients with low CrCl were older and had more comorbidities. Low CrCl was associated with higher risks of NACE (hazard ratio [HR], 1.72; 95% confidence interval [CI], 1.19–2.49; p=0.004), ischemic events (HR, 2.70; 95% CI, 1.09–6.70; p=0.032), and bleeding (HR, 1.54; 95% CI, 1.01–2.34; p=0.046).

Edoxaban monotherapy reduced NACE compared with dual therapy in both the low CrCl group (12.1% vs 21.7%; HR, 0.52; 95% CI, 0.28–0.98; p=0.042) and the high CrCl group (5.2% vs 14.5%; HR, 0.40; 95% CI, 0.25–0.65; p<0.001), with no significant interaction by renal function (p=0.53).

These findings suggest that edoxaban monotherapy was associated with lower NACE risk than dual antithrombotic therapy regardless of renal function in patients with AF and stable CAD.